Therapeutic composition



is complete.

Patented Dec. 23, 1941 THERAPEUTIC'COMI'OSITION Richard 0.,Roblin, Jr., Old Greenwich, Conn., as-

signor to American Cyanamid Company, New York, N. Y., a corporation of Maine 4 No Drawing. Application March 15, 1939, Serial No. 261,976

3 Claims.

' du'ce irritation or necrosis when injected.

It is one of the objects of the present invention to prepare solutions of calcium salts which are therapeutically useful. It is another object to prepare stabilized aqueous solutions of such calcium salts of high concentration. It is a still further object to prepare stabilized solutions which are free from irritant and toxic properties.

These and other objects are attained by dissolving in water'a sufiicient quantity of a calcium salt having the following structural formula wherein R represents H, CH3 or C2H5 or CsH-z, R represents CH3, C2H5 or C3H'z, and where R and R together contain at least 2 C atoms, such solution being stabilized by the addition of suitable stabilizing agents.

The following is one specific example illustrating the present invention which, however, is not restricted to the specific details shown.

A solution may be prepared by dissolving 100 pounds of calcium alpha-hydroxyisobutyrate in 500 pounds of boiling water. After the calcium salt has been dissolved but while the solution is still hot, there are added 20 pounds of boric acid, preferably with suitable agitation until solution There results a' substantially neutral solution which is stable, even at low temperatures, and is suitable for use in the treatment of various animals for'calcium deficiency.

The solution may be placed in sealed ampoules and sterilized in a well-known manner. If desired a preservative may be added to the solution to maintain the solution aseptic. Another method by which the solution may be steriliz ed i s i)y. passing the hot solution through a Berkefeld filter whereupon the filtrate is placed in suitable ditions.

In the specific example about 3.2% of boric acid by weight is used for stabilization. This amount may be varied widely but I have found that 1% to 5% of boric acid is generally sumcient for my purposes. In place of boric acid as the stabilizing medium, I may also utilize other substances such as urea, aluminum chloride, calcium saccharate and similar materials, taken alone or in combination with each other or with boric acid. The amounts of such materials used may be varied in accordance with the various requirements and the effectiveness of the stabilizer. For example, when urea is utilized for stabilization, about 5% to 10% of ureais sufiicient.

In place of the calcium alpha-hydroxyisobutyrate I may use the calcium salts of such acids as on-hYdlOXY-ll-blltYIlC acid, a-hydroxy-u-methyln-butyric acid, a-hydroxy-a-ethyl n-butyric acidor ahydroxy-a-methyl-n-valeric acid like.

The strength of the solutions prepared may vary over a wide range although it is generally desirable to prepare a solution which is as concentrated as possible and which is still stable under the various conditions of storage and use. Calcium alpha-hydroxyisobutyrate, for instance, is.normally soluble in water to the extent of 10% to make a saturated solution but, by use of the stabilizing media as described above, it is possible to prepare much more concentrated solutions which may be referred to as supersaturated solutions. Thus I may prepare solutions which may contain as high as 40% of the calcium salt and and the these solutions may be maintained for long periods of time. Since the calcium salts which I use contain a high percentage of calcium, I can prepare compositions of similar concentration mav also include other substances having thera- Thus I may peutic value in the compositions. add to the stabilized solutions various other soluble compounds such as alkaloids, various salts of e the alkali and alkaline earth metal group, me-

- sterile containers and is sealed under sterile con-- 05 tallic salts, dyestuffs or other organic compounds useful in chemotherapy, glucocides, local anaes thetics and the like. It is only necessary that the additional compounds which are utilized be sumciently soluble to permit their use in the compositions described and further, that they be 8111,- flciently stable to permit their incorporation into any compositions.

It will be obvious that suitable changes and variations may be made in my invention without departing from the spirit and scope thereof except as defined in the appended claims.

I claim: 1. A therapeutic composition comprising a stable aqueous solution of about 1% to 5% of boric acid and at least 16% calcium alpha-hy droxyisobutyrate.

2. A therapeutic composition comprising a stable aqueous solution of about 3.2% of boric acid and at least 16% calcium alpha-hydroxyiso- I butyrate.

wherein R represents a member of the group consisting of H, CH3, CcHs and CaHl, R represents a member or the group consisting of CH3, CrHs and C3H'1, and where R and R together contain at least 2 C atoms.

RICHARD O. ROBLIN, JR. 

